Previous investigations will be extended into the experimental neuropathology of the optic nerve. There are few available laboratory models of optic nerve disease. Nevertheless optic nerve disorders are highly prevalent among humans and there is a need to understand mechanisms that may underly their development. Rats will be used exclusively in the studies, and the tissues will be examined by light microscopy (using histochemical and standard staining techniques), and by electron microscopy. In addition, the vascular changes will be evaluated using injection and clearing methods and histochemical stains that demonstrate capillary endothelium. The intoxications will be studied in chronically exposed animals and the anterior visual system will be examined sub-serially. Investigations into the neuropathology of cyanide intoxication will be extended. The characteristics of ethambutol intoxication will be investigated. Lead intoxication will be studied in weanling rats. Previous studies have shown that adult rats are not susceptible. An attempt will be made to understand the role of 5' nucleotidase in the function of the adult optic nerve by intoxicating animals with nickel, a known inhibitor of this enzyme.